Linkage disequilibrium between tumor necrosis factor (TNF)-α–308 G/A promoter and TNF-βNco I polymorphisms: Association with TNF-α response of granulocytes to endotoxin stimulation

Abstract

A linkage disequilibrium between the two TNF polymorphisms was found. This study revealed a significant association between genotype and phenotype for both TNF polymorphisms. Heterozygosity for both TNF polymorphisms is associated with an increased TNF-alpha response.

Rapid Genotyping for Tumor Necrosis Factor-α (TNF-α) −863C/A Promoter Polymorphism That Determines TNF-α Response

“…The allele frequencies found in our study for the three TNF polymorphisms were in agreement with those reported in previous studies (11,16 ). We also demonstrated that the Ϫ863 C/A polymorphism is associated with the TNF-␣ response of human whole blood of healthy volunteers to endotoxin stimulation.…”

“…Genotyping for the TNF-␣ Ϫ308 and the LTA NcoI genetic polymorphisms was carried out as described previously (16 ). Because a previously described assay for genotyping for the TNF-␣ Ϫ863 polymorphism (11 ) is time-consuming and requires several manual steps, we developed a real-time PCR assay with specific fluorescently labeled hybridization probes.…”

Novel polymorphisms and the definition of promoter ‘alleles’ of the tumor necrosis factor and lymphotoxin α loci: inclusion in HLA haplotypes

“…18,23,40,58,63,66 When associations of individual SNPs among the TNF and LTA alleles were examined in this study, only a single association was observed. In each of the alleles described, the LTA SNP À293A was always found in association with LTA þ 81A and LTA þ 369C, while the LTA SNP À293G was always found associated with LTA þ 81C and LTA þ 369G.…”

“…For example, an association could be assigned between the SNPs TNF À308A, LTA þ 253G (NcoI RFLP; TNFB*1) and LTA þ 724A, which has been observed by others. 23,25,27,28,40 Interestingly, each of these SNPs generally have been associated with higher production level phenotypes of both TNF and LTA, with the 8.1 ancestral HLA haplotype …”

“…27,28,[30][31][32][33][34][35] On the other hand, there have been numerous studies, which have correlated specific SNPs to TNF and to LTA expression levels in groups of individuals and from cell lines, but with varying results. [36][37][38][39][40] It is understood that the production level phenotype of an individual cytokine can have a major impact on immune responsiveness, and an abundance of studies have linked specific SNPs to disease. 41,42 As examples, TNF and LTA expression levels and SNPs have been shown to correlate with an individual's susceptibility to, severity of and/or prognosis of diseases such as HIV, multiple sclerosis and cerebral malaria [43][44][45][46] and with prognosis or outcome of allograft transplantation and malignancies.…”